The Potential of Butyric Acid as an Alternative Treatment for Parkinson’s Disease

April 26, 2018

Parkinson’s disease, which affects more than 10 million people worldwide, extracts a terrible toll on patients and caregivers alike. Throughout the course of the disease, patients’ fundamental motor skills deteriorate in an all-too-familiar march toward incapacitation. Meanwhile, patients experience a debilitating array of cognitive problems that mirror dementia as the central nervous system neurons deteriorate further. This leads to severely compromised functionality, diminished quality of life, and ever-increasing dependence on others for basic needs and safety.

Unfortunately, Parkinson’s disease is currently incurable and conventional pharmacological treatments for Parkinson’s disease primarily attempt to treat the neurochemical deficits that are characteristic of the disease using chemicals like levodopa (L-DOPA), which are deficient in Parkinson’s patients. Though scientists are investigating innovative emerging interventions like gene therapy to help patients, the current standard of care only delays the inevitable, As a result, a growing number of clinicians and patients are turning to alternative treatment in hope of alleviating symptoms. Currently, one such option is proving to be particularly promising: butyric acid.

Understanding Butyric Acid as an Alternative Treatment for Parkinson’s

Butyric acid is a natural molecule produced by the human body and found in high concentrations in the gut. Physiologically, butyric acid has a handful of purposes ranging from cell signaling to regulating inflammation, which suggests potential therapeutic benefit for Parkinson’s patients. Indeed, several researchers have connected the protective and restorative abilities of chemicals like butyric acid to a reduction of Parkinson’s symptoms though these have stopped short of a full explanation of mechanisms.

In 2014, a groundbreaking theoretical synthesis by Drs Chandramohan Wakade and Raymond Chong investigated the neuroprotective mechanisms of butyric acid in the context of Parkinson’s disease by analyzing the relationship between the niacin receptor and dopamine levels. Through their synthesis, the researchers propose that butyric acid has the potential to beneficially impact Parkinson’s symptoms and underlying pathology via no fewer than three distinct mechanisms: reducing inflammation, increasing dopamine synthesis, and boosting mitochondrial function to provide cells with more energy. As such, patients seeking to augment their Parkinson’s treatment regimen would be well advised to carefully examine this emerging therapy to gain a greater understanding of its promise. In particular, Wakade and Chong’s research offers a compelling introduction to the concept of butyric acid as a treatment for Parkinson’s.

Controlling Inflammation

Reducing inflammation is the most immediate benefit that butyric acid offers to Parkinson’s patients. In the gut, butyric acid controls inflammation by signaling white blood cells to stand down and refrain from secreting proinflammatory molecules such as nuclear factor kappa light chain enhancer of activated B cells (known ubiquitously as NF-kB) and tumor necrosis factor alpha (TNFa). Additionally, butyric acid can be used as a substitute for other physiological anti-inflammatory molecules, which means that if these other molecules are in short supply, a butyric acid molecule in the right spot could compensate for this deficit and allow for normal function. Though these effects are known to occur in the gut, it is as of yet unknown if they occur in the brain as well. Nonetheless, the researchers are optimistic that the effects will carry over to the brain to produce a therapeutic benefit. Of particular interest to Parkinson’s patients, Wakade and Chong’s synthesis argues that butyric acid can stand in for niacin to address the neuroinflammation associated with the disease.

Niacin is a common nutrient with an array of physiological purposes, some of which overlap with butyric acid. Critically, niacin receptors on immune cells act as a brake pedal for inflammation; so long as the niacin receptors are occupied by niacin molecules, the cells don’t secrete inflammatory molecules. Likewise, when niacin is absent, there’s no foot on the brake pedal and inflammation occurs. However, the niacin receptor is highly expressed on immune cells, and butyric acid can bind to the niacin receptor just as easily as niacin can. Using this logic, the authors of the synthesis argue that butyric acid’s impact on these immune cells will be similar to niacin’s, preventing inflammatory responses.

This has important implications for Parkinson’s patients, as niacin is often depleted as a consequence of Parkinson’s treatment and, some believe, the disease itself; when niacin is depleted, the niacin receptors on white blood cells remain empty, causing inflammation—and inflammation is associated with both the emergence and severity of Parkinson’s symptoms. In fact, one study linked regular use of anti-inflammatory drugs with a 29% reduced chance of developing Parkinson’s disease in the first place. Controlling neuroinflammation with butyric acid could thus directly alleviate some of the motor difficulties, diminished concentration, and depression that patients experience.

Improving Dopamine Synthesis

While treating inflammation may be a critical part of Parkinson’s treatment for many, it is only addressing the symptoms of the Parkinson’s pathology; patients are still ill even if their inflammation is under control. Dopamine synthesis, on the other hand, is independent of inflammation and an even more fundamental aspect of Parkinson’s disease. As such, Wakade and Chong argue, the primary benefit of butyric acid is its ability to revitalize dopamine synthesis, addressing the underlying pathology of Parkinson’s rather than the symptoms alone.

Niacin is a chemical precursor to dopamine, which means that it’s a critical nutrient in the context of Parkinson’s disease. The Parkinson’s pathology results in heavily depleted dopamine within the brain, which ultimately causes many of the disease’s most visible symptoms such as motor difficulties. The current approach to treating this dopamine deficiency is administration of L-DOPA, a precursor of dopamine that requires one metabolic step to turn into dopamine. However, L-DOPA is far from perfect and only a portion of the chemical makes it into the patient’s bloodstream after metabolizing.

According to Wakade and Chong, intervening earlier in the dopamine synthesis pathway is thus potentially beneficial. Niacin’s role in dopamine synthesis occurs prior to L-DOPA and is thus a precursor of other precursors to dopamine. Butyric acid can improve the amount of free niacin that is available for dopamine synthesis in much the same way that it controls inflammation; when butyric acid molecules bind to the niacin receptor instead of niacin, more niacin is free to be incorporated into the dopamine synthesis pathway. Ultimately, the newly freed niacin is used to make dopamine, which means that the symptomology behind Parkinson’s is addressed in multiple dimensions with the same chemical.

Resupplying The Mitochondria

The final mechanism of butyric acid that would be beneficial to Parkinson’s patients is the stimulation of the mitochondria, which are dysfunctional in Parkinson’s patients due to niacin deficiency. Niacin is a precursor of the cellular energy molecules nicotinamide adenine dinucleotide (NAD) and NAD’s oxygen-reduced format, known as NADH. These molecules are used by the mitochondria to create chemical sources of energy for the cell. In the event of NAD and NADH deficiency, the mitochondria can’t perform their functions as effectively, which causes metabolic chemicals like fumarate and excess hydrogen atoms to build up and cause significant mitochondrial damage. Over time, this damage becomes debilitating and reduces the mitochondria’s function further, as established by other researchers.

Wakade and Chong argue that the mitochondrial dysfunction caused by NAD and NADH deficiency is implicated in the negative symptoms of Parkinson’s such as depression and reduction of fine motor control. Though other pathologies within Parkinson’s disease account for these symptoms more directly than mitochondrial dysfunction does, NAD and NADH are also essential in many metabolic processes, including the synthesis of dopamine. Once again, butyric acid could prevent this damage from occurring or allow cells to compensate after the fact, potentially reducing Parkinson’s symptoms and protecting patients from further deterioration.

The Critical Role of Bioavailability

Butyric acid offers exciting possibilities for patients struggling with Parkinson’s, making it an attractive option for those seeking effective and well-tolerated alternatives to conventional treatment. However, patients who want to add butyric acid to their treatment plans need a supplement that can overcome the body’s natural barriers. Like L-DOPA, butyric acid can cross the blood-brain barrier once it’s soluble in the bloodstream. Unfortunately, it suffers a large amount of attrition via first pass metabolism prior to that point. As a result, only a fraction of the butyric acid ingested makes it to cells in the brain where it is needed. Thus, supplements that don’t improve butyric acid’s ability to survive first pass metabolism won’t be sufficient.

Though this obstacle is substantial, recent breakthroughs in the generation of high-bioavailability drug delivery mechanisms have opened the door to effective supplementation with butyric acid. These breakthroughs have given patients the opportunity to treat their Parkinson’s with a natural supplement which has few side effects and a substantial amount of evidence indicating its efficacy in addressing multiple dimensions of Parkinson’s disease. Should patients seek to bolster their conventional Parkinson’s treatment with a supplement which has the potential to treat both the core pathology of the disease and its symptoms, a highly bioavailable butyric acid supplement is a promising place to start.

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